{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:20:59Z","timestamp":1790688059777,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:p>Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the<jats:italic>LMNA<\/jats:italic>gene, is characterized by post\u2010natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which<jats:italic>LMNA<\/jats:italic>mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP\u20109, \u20102, \u20103, \u20108 and \u201013, and found that only the 82 kDa active enzyme forms of MMP\u20109 are significantly higher in MADA sera compared with healthy controls (<jats:italic>n\u2003<\/jats:italic>=\u200316). The serum level of MMP\u20103 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP\u20102, \u20108 and \u201013 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP\u20109. Similarly, normal serum levels of tumour necrosis factor alpha (TNF\u2010\u03b1), interleukin (IL)\u20106 and IL\u20101\u03b2 were detected. These data suggest a possible involvement of MMP\u20109 in MADA disease, underlying the potential use in diagnosis and therapy.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2008.01034.x","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T10:26:27Z","timestamp":1232706387000},"page":"374-383","source":"Crossref","is-referenced-by-count":19,"title":["Increased release and activity of matrix metalloproteinase\u20109 in patients with mandibuloacral dysplasia type A, a rare premature ageing 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